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DiscoveRx has developed a unique assay technology based on an enzyme-coupled detection system that measures ADP accumulation which has been widely applied for kinetic studies of proteins that utilize ATP, GTP or UTP. The kinetic assay format offers a number of benefits for kinase and ATPase research in particular, including a broad tolerance to additives, no need for a modified substrate, the a...
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DiscoveRx has developed a novel application of our established Enzyme Fragment Complementation (EFC) technology that allows us to monitor protein-protein interaction events in whole cells. Using this approach, we have designed the PathHunter® Arrestin assay that monitors arrestin binding to activated GPCRs. The activity is subsequently detected with a single addition, HTS friendl...
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There are numerous assays available to measure the activity of enzymes involved in the transfer of a phosphate from ATP to a substrate macromolecule. However, there are only a few assays for enzymes that utilize other nucleotide triphosphates, opening opportunities to address pharmacologically relevant targets.
GTPases are a broad family of enzymes with a wide variety of activitie...
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Kinase targets have been extensively studied in biochemical assays using purified protein fragments for the kinase and the substrate. However, there is an increasing need to understand how kinases function in the context of a whole cell assay. DiscoveRx has pioneered a protein interaction assay system using our established Enzyme Fragment Complementation (EFC) β-Galactosidase detection sys...
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The cAMP Hunter eXpress GPCR Assay can be used for small or large molecules. The kits provide a robust, highly sensitive and easy-to-use assay for monitoring G-protein coupled receptor (GPCR) activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells.
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cAMP Hunter Cell Lines are non-force-coupled Gs and Gi stable clonal cell lines that expedite drug screening by providing robust responses, with accurate pharmacology. They provide the means for the measurement of an ubiquitous second messenger (cAMP) to determine the mechanism of action of ligands. Each cell line has been characterized for its appropriate GPCR...
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GPCR activation results in G-protein dependent events such as second messenger signaling, as well as initiation of a host of cellular responses that regulate function and activate alternative pathways that are independent of G-protein activation. Recent studies have highlighted the importance of G-protein independent signaling in normal and pathogenic tissue physiology. Two of the w...
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DiscoveRx has developed a panel of over 30 naturally Gq-coupled or dual coupled GPCR/Arrestin cell lines that can be used in screening and profiling applications for both arrestin biology and calcium based signaling. This presents a number of interesting use case scenarios, such as sequential monitoring of both readouts in a single screen, or use of the same cell line for analysis of bot...
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The EFC BlocDetect Kit is used to identify compounds that inhibit beta-galactosidase complementation or beta-galactosidase activity. As described below, beta-galactosidase complementation is DiscoveRx’s core technology for both cell-based as well as biochemical assays. The assay has been validated for use in both 96-well and 384-well microplate formats....
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Kinase targets have been extensively studied in biochemical assays using purified protein fragments for the kinase and the substrate. However, there is an increasing need to understand how kinases function in the context of a whole cell assay. DiscoveRx has pioneered a protein interaction detection system using well-established Enzyme Fragment Complementation (EFC) technology, by monitoring the...
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Kinase targets have been extensively studied in biochemical assays using purified protein fragments for the kinase and the substrate. However, there is an increasing need to understand how kinases function in the context of a whole cell assay. DiscoveRx has pioneered a protein interaction detection system using well-established Enzyme Fragment Complementation (EFC) technology. We show here that...
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The cAMP detection technologies are widely used in high throughput screening (HTS) for measuring a functional response of a GPCR consequent to ligand-binding. However, a robust and sensitive cAMP detection platform that allows one to differentiate a full agonist from a partial agonist or an antagonist response from an inverse agonist response while also being able to identify allosteric compoun...
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The PathHunter™ technology from DiscoveRx is an adaptation of Enzyme Fragment Complementation (EFC) that provides a novel, generic cell-based assay format for detecting protein-protein interactions. This approach has enabled development of a number of new screening and profiling assays for targets that have been difficult to address in a cell-based assay. One such class of targets, the re...
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DiscoveRx® has pioneered a novel enzyme complementation system to monitor cellular events such as protein translocation, protein interactions, and degradation in an HTS friendly, cell-based format. This unique technology provide a basis for the generation of novel cellular assays for intractable targets, and simplify the detection of cellular s...
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PathHunter® Cytosolic Tyrosine Kinase (CTK) Activity Assays are functional cell-based assays used for identification, screening or profiling of small molecule inhibitors. These assays cannot be used for functional testing of biologics.
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PathHunter® Activated GPCR Internalization Assays are non-imaging, non-antibody based chemiluminescent detection assays that provide a direct and quantitative measurement of internalized GPCRs localized to early endosomes. This allows the internalization of GPCRs to be quantitatively measured in live cells without the need for expensive microscop...
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The PathHunter Detection Kit is to be used with PathHunter Cell Lines or cell lines made with ProLabel/ProLink expression or cloning vectors. The kit is easy-to-use and has been successfully run in both 96-well and 384-well microplate format. The resulting signal is chemiluminescent and is read with any standard plate reader. PathHunter products utilize the Enz...
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PathHunter® eXpress Activated GPCR Internalization Assays are ready to use complete kits that contain everything you need to measure arrestin bound internalized GPCRs in live cells without the hassle of using antibodies, radioactivity or elaborate imaging. The eXpress kits include single use vials of frozen cells stably expressing the GPCR of int...
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PathHunter® eXpress Cytosolic Tyrosine Kinase (CTK) Functional Assay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay for monitoring cytokine receptor activation or cytosolic tyrosine kinase inhibition. The eXpress kits contain everything needed for a complete CTK experiment including cells, detection reagents,...
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PathHunter® eXpress Nuclear Hormone Receptor (NHR) Functional Assay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay for monitoring NHR activation, translocation and recruitment of coactivator/corepressor proteins. The eXpress kits contains all the reagents needed for a complete NHR experiment including cells...
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PathHunter® eXpress Receptor Tyrosine Kinase (RTK) Functional Assay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay for monitoring receptor tyrosine kinase activation, phosphorylation and recruitment of SH2
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PathHunter® eXpress Total GPCR Internalization Assays are ready to use complete kits that contain everything you need to measure internalized GPCRs in live cells but without imaging, antibodies or radioactivity. The eXpress kits include single use vials of frozen cells stably expressing the GPCR of interest, optimized cell plating reagent, chemiluminescent detection reagents and ...
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PathHunter β-Arrestin cell lines are stable clonal cell lines that expedite drug discovery and development by providing robust response to over 90% of all known G-protein coupled receptor (GPCRs), with accurate pharmacology. This assay measures an essential pathway in GPCR activation, i.e., β-arrestin recruitment to activated GPCRs, enabling scientist...
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PathHunter® GPCR Explorer kits are a simple and easy-to-use method for building on-demand functional GPCR assays. Whether you have a panel of mutant GPCR cDNAs, a favorite ortholog GPCR or a GPCR heterodimer you’d like to funct...
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PathHunter Receptor Tyrosine Kinase (RTK) Functional Assays are functional cell-based assays used for identification, screening or profiling of agonists, small molecule inhibitors and therapeutic biologics (peptides, proteins and various types of antibodies). Additionally, they have non-R&D applications as bioassays for QC testing and testing for anti-drug ...
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PathHunter® Total GPCR Internalization Assays are non-imaging, non-antibody based chemiluminescent detection assays that provide a direct and quantitative measurement of internalized GPCRs localized in early endosomes. This allows the internalization of GPCRs to be quantitatively measured in live cells with-out the need for expensive microscopy. The PathHunter system combines eng...
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Kinase therapeutics includes both monoclonal antibodies (mAbs) and small-molecule inhibitors. DiscoveRx’s PathHunter® protein: protein interaction system uses well-established Enzyme Fragment Complementation (EFC) technology by monitoring interaction of target proteins with SH2 phosphotyrosine binding domains. We demonstrate application of PathHunter® cell-ba...
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The PathHunter® EA Detection Kit is used with PathHunter Cell Lines that express the Enzyme Acceptor (EA) fragment of beta-galactosidase, such as EA-Nuc, EA-Cyto, or EA-beta-Arrestin Parental Cell Lines. This detection reagent formulation includes ED reagent, a small ProLabel-type peptide that complements with EA during assay incubation. The as...
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The PathHunter Flash Detection Kit is to be used with PathHunter Cell Lines or cell lines made with ProLabel®/ProLink™ expression or cloning vectors. The kit is easy-to-use and has been successfully run in both 96-well and 384-well microplate format. The resulting signal is chemiluminescent and is read with any standard plate reader.
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The PathHunter® ProLabel® Detection Kit is for use with PathHunter Cell Lines expressing ProLabel (PL) or ProLink™ (PK) expression or cloning vectors. The kit measures the total amount of ProLabel- or ProLink-tagged protein expressed in cells. The assay can be used in both 96-well and 384-well ...
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Orphan GPCRs continue to represent a target class with immense potential for the discovery of novel therapeutic compounds. In spite of the proven track record of GPCRs as druggable targets, over 100 non-odorant GPCRs remain to have their cognate ligands identified. Here we present the PathHunter® Arrestin assay as a facile screening approach to orphan GPCR drug discovery. In this...
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DiscoveRx previously introduced a protein-protein interaction system using enzyme fragment complementation that provides a robust, HTS friendly format for monitoring the interaction of activated GPCRs and β-arrestin. To date, DiscoveRx has applied this technology to generate over 170 pre-validated human cell lines. More recently, the coupling of mouse and rat GPCRs in the arrestin signalin...
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The ProLink™ Detection Kit, a member of the Synergy Product Line, is used to confirm expression of ProLink-tagged proteins. ProLink (PK or ED) is a component of DiscoveRx’s β-gal complementation technology and is used to engineer all PathHunter® protein-protein interaction cell lines, including β-Arrestin GPCR cell lines, ...
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DiscoveRx's PathHunter® platform is a simple, cell-based, chemiluminescent assay format that allows for screening large numbers of small molecules or hybridoma supernatants in a one-step, no-wash format making it both user-friendly and HTS-compatible. In this study, we demonstrate the 3456- and 1536-well application of DiscoveRx's PathHunter GPCR β-...
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DiscoveRx has developed a panel of over 120 characterized GPCR cell lines that monitor receptor activity using interaction with human β-Arrestin. These cell lines have numerous applications in both high throughput screening and downstream compound analysis, and have now been successfully adopted by a number of pharmaceutical and biotechnology companies. A relatively recent application for ...
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As more is learned about the intricacies of GPCR signaling, the harder it becomes to accurately describe ligand activity using a single functional readout. It is now well appreciated that GPCR activation results in G-protein dependent as well as G-protein independent signaling events such as β-arrestin recruitment and internalization. The complex relatio...
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The Human Kinome is an artistic representation of the human kinome phylogenetic tree based on extensive published research and recently annotated to include lipid, atypical and clinically-relevant mutant kinases. For the eight protein kinase groups depicted in the main dendrog...
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InCELL Hunter™ Bromodomain Cell-Based Assays, when used in conjunction with a InCELL Hunter Detection Kit (96-0002, 96-0002L or 96-0002XL), provides a cell based assay to look at protein stability upon compound binding. The assay described in this booklet have been validated for use in 384-well microplate formats.
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The DiscoveRx Ca NWPLUS Assay Kit provides a fast, reliable method for detection of changes in intracellular calcium. Cells expressing a receptor of interest that signals through calcium are pre-loaded with a calcium-sensitive dye and then treated...
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We tested the interaction of 72 kinase inhibitors with 442 kinases covering >80% of the human catalytic protein kinome. Our data show that, as a class, type II inhibitors are more selective than type I inhibitors, but that there are important exceptions to this trend. The data further illustrate that selective inhibitors have been developed against the majority of kinases targeted by ...
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Assays that directly detect compound binding inside cells can be of great utility in translating in vitro data to more biologically relevant models. However, these types of intracellular binding assays have not been possible so far. Cellular assays for serveral targets are limited to downstream activity-based readouts which can be difficult to develop, may not be proximal to the target, or may ...
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Inhibitor association and dissociation kinetics can have important effects on a compound’s drug-like properties and in vitro, cellular, and in vivo behaviors. The association and dissociation rates for protein target-inhibitor complexes are variable and can be both inhibitor and protein-dependent. In addition, it is often important to classify inhibitors as being reversible or irreversibl...
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Post-translationally appended acetyllysine marks on histone tails are key regulatory features of the epigenetic code. Bromodomains are “readers” of this specific lysine acetylation code, playing an important role in chromatin remodeling and regulation of gene expression. Bromodomains have emerged as an important new druggable target class in small-molecule inhibitor drug discovery, ...
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We have applied a panel of primary human cell-based in vitro systems (the BioMAP® systems platform) that model complex aspects of disease and tissue biology to investigate the biological mechanisms that underlie certain drug adverse effects. Here we present the analysis of several anti-inflammatory kinase inhibitors in development, including inhibitors of Jak kinase (tofacitinib) and syk ki...
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The recent appreciation of functional selectivity/ligand bias in GPCR signaling has uncovered new opportunities for therapeutic discovery and continues to increase our understanding of compound function. We reasoned that since ligands and hence receptor conformation can differentially stimulate particular signaling pathways, variations in amino acid composition could similarly bias receptors an...
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Assays that directly detect compound binding inside cells can be of great utility in translating in vitro data to more biologically relevant models. However, these types of intracellular binding assays have not been possible so far. Cellular assays for these targets are limited to downstream activity-based readouts which can be difficult to develop, may not be proximal to the target, or m...
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THE CHALLENGE
Our client, a global integrated pharmaceutical company, entered the lead optimization stage with three p38MAPK antagonists. All three compounds were competitive inhibitors for ATP binding and indicated to treat rheumatoid arthritis (RA). At the time the client approached BioSeek, data from biochemical p38MAPK assays and THP1 monocyte cell-line-based assays were generated but...
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CHALLENGE
The client identified a novel IL-17 inhibitor as its lead compound to treat an autoimmune disease. Specifically, it had identified the compound in a phenotypic screen of mouse cells and tested it in a rodent model for Collagen-Induced Arthritis. At this point, our client had collected valuable pre-clinical insights about the efficacy of the compound based on cellular and biochem...
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THE CHALLENGE
Our client, a global integrated pharmaceutical company, had completed Phase I studies with an investigative therapeutic, Drug A, for a cancer indication. In the Phase I study, a small number of patients experienced a specific serious adverse event (AE). This AE was correlated with the patients’ recent use of a second and unrelated therapeutic, Drug B. While Drug B was ...
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THE CHALLENGE
The client was a global pharmaceutical company interested in adding therapeutics for benign prostatic hyperplasia (BPH) to its development pipeline, searching for opportunities outside the currently approved classes of BPH drugs.
Certain adrenergic receptor (AR) antagonists were already marketed to treat the urinary retention symptoms of BPH. Additional observat...
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Ubiquitin-mediated degradation of signaling proteins is a primary means of signal regulation in a wide variety of cellular processes including inflammatory signaling, DNA damage responses, developmental pathways, and the cell cycle. However, observation of these events with the throughput necessary for modern drug discovery has been challenging. Numerous reporter proteins exist that can be used...
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Epigenetics can be defined as inheritable alterations in gene expression that arise independently of DNA sequence changes. Despite its relative infancy, the emergence of druggable targets that impact epigenetic signaling has the potential to serve as a new and exciting strategy to the treatment of human diseases including cancer, autoimmune and metabolic diseases.
At DiscoveRx, we have de...
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Assays that directly detect compound binding inside cells can be of great utility in translating in vitro data to more biologically relevant models. However, these types of intracellular binding assays have not been possible so far. Cellular assays for serveral targets are limited to downstream activity-based readouts which can be difficult to develop, may not be proximal to the target...
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Post-translationally appended acetyl-lysine marks on histone tails are key regulatory features of the epigenetic code. Bromodomains are “readers” of this specific lysine acetylation code, playing an important role in chromatin remodeling and regulation of gene expression. Bromodomains have emerged as an important new druggable target class in small-molecule inhibitor drug discovery,...
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Monoclonal antibodies (MAbs) represent one of the fastest growing classes of biotherapeutic molecules today. While many technologies exist for generating and panning large collections of antibody fragments, there is a clear need for tools that can reliably detect both the binding and functional activity of a monoclonal antibody in a fast, reproducible and cost effective manner. This requires va...
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Development of drugs that target epigenetic signaling mechanisms is a new and exciting strategy for the treatment of cancer. Epigenetic processes including chemical modifications to DNA and also to the histone proteins that package the DNA in chromatin play a central role in gene expression and regulation. One of the most frequently occurring modifications is...
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PathHunter® Pathway Assays, when used in conjunction with the respective detection kit (indicated in the target specific data sheet) provide a cell-based functional assay to study various protein activities in a cell. The assays described in this booklet have been validated for use in 384-well microplate formats.
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The PathHunter ProLabel/ProLink Detection Kit is to be used with PathHunter Cell Lines or cell lines made with ProLabel/ProLink (PL/PK) expression or cloning vectors. The kit is easy-to-use and has been successfully run in both 96-well and 384-well microplate format. The resulting signal is chemiluminescent and is read with any standard plate reader.
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Monoclonal antibodies (MAbs) represent one of the fastest growing classes of biotherapeutic molecules today. While many technologies exist for generating and panning large collections of antibody fragments, there is a clear need for tools that can reliably detect both the binding and functional activity of a monoclonal antibody in a fast, reproducible and cost effective manner. This requires va...
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Presentation given on 28 October 2013 at CHI's Fast Congress on Phenotypic Drug Discovery, Cambridge, MA
Abstract
Phenotypic drug discovery (PDD) is a target agonistic approach using biological systems to screen for new drugs. Primary human cells are useful for PDD as they can be incorporated into high throughput assays but are more physiologically ...
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Background/Purpose
Proinflammatory cytokines cause joint inflammation and destruction in rheumatoid arthritis (RA) as exemplified by the therapeutic success of inhibiting tumor necrosis factor alpha (TNFa) by adalimumab (ADA) and interleukin (IL)-6 receptor (IL-6R) by tocilizumab (TCZ). Such biologics and small molecule inhibitors, including methotrexate (MTX) and ...
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Improving the safety of drug candidates that enter clinical development requires assays that are more predictive of human outcomes. The BioMAP platform uses human primary cells to model complex aspects of disease and tissue biology and can be applied to better understand biological mechanisms that underlie drug efficacy and safety. Here we test Ibrutinib, a BTK inhibitor recently ap...
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The pattern of intracellular signaling downstream of GPCR activation is now known to be specific to the ligand-receptor pair as opposed to an inherent, rigid property of the receptor. In a drug discovery setting, this property of GPCRs is now being exploited to develop designer molecules that have tailored intracellular responses. Although pathway bias is typically associated with synthetic mol...
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Ligand-induced receptor dimerization is the first functional step in receptor activation, representing the most proximal, functional read-out for receptor activation. For the majority of Receptor Tyrosine Kinases these are homomultimer events whereas for cytokine receptor and other cell surface kinases these are typically heteromultimeric events. Standard cellular protein interaction techniques...
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Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination therapies, which can pose significant clinical development challenges. Epigenetic reader domai...
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Background/Purpose: Proinflammatory cytokines cause joint inflammation and destruction in rheumatoid
arthritis (RA) as exemplified by the therapeutic success of inhibiting tumor necrosis factor alpha (TNFa) by
adalimumab (ADA) and interleukin (IL)-6 receptor (IL-6R) by tocilizumab (TCZ). Such biologics and small
molecule inhibitors, including methotrexate (MTX) and the recentl...
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SLAS2014 presentation by Dr. Ellen Berg describing some of the challenges encounted in extracting meaningful data
Agenda slide
Problem
Drug discovery productivity is at an all time low
We are swimming in oceans of data
High throughput technologies
New assay models and platforms
Needed
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Improving the safety of drug candidates that enter clinical development requires assays that are more predictive of human outcomes. The BioMAP® platform uses human primary cells to model complex aspects of disease and tissue biology and can be applied to better understand biological mechanisms that underlie drug adverse effects. Here we present the analysis of several anti-inflammatory kina...
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PathHunter® Cytosolic Tyrosine Kinase (CTK) Functional Assays are functional cell-based assays used for identification, screening or profiling of agonists, small molecule inhibitors and therapeutic biologics (peptides, proteins and various types of antibodies). Additionally, they have non-R&D applications as bioassays for QC testing and testing for anti...
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PathHunter Receptor Tyrosine Kinase (RTK) Activity Assays are functional cell-based assays used for identification, screening, or profiling of small molecule inhibitors. This assay format cannot be used for functional testing of biologics.
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PathHunter® Receptor Tyrosine Kinase (RTK) Internalization Assays are nonimaging, non-antibody based chemiluminescent detection assays that provide a direct and quantitative measurement of internalized RTKs localized to early
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DiscoveRx has pioneered a novel enzyme complementation system to monitor cellular events such as protein translocation, protein interactions, and degradation in an HTS friendly, cell-based format. This unique technology provide a basis for the generation of novel cellular assays for intractable targets, and simplify the detection of cellular signaling events using a simple one-step chemil...
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cAMP Hunter Exenatide Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study Exenatide potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qualifie...
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Drug induced liver injury, in particular the idiosyncratic type (IDILI), is
extremely difficult to identify before a compound reaches the later stages of drug development, often not being detected until the clinical trials or
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Addressing safety aspects of drugs and environmental chemicals relies extensively on animal testing. However the quantity of chemicals needing assessment and challenges of species extrapolation require development of alternative approaches...
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The ToxCast and Tox21 programs have generated in vitro screening data
for over 1000 chemicals to aid in hazard identification and setting chemical testing priorities. These data, together with high-throughput
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Introduction. There is increasing interest in applying in vitro methods to characterize the potential toxicity of drugs and chemicals. Methods that would allow automatic classification of in vitro activity profiles into mechanism classes could be helpful in prioritizing novel agents.
<...
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Ligand-induced receptor dimerization is the first functional step in receptor activation, representing the most proximal, functional read-out for receptor activation. Here we present a novel application of the Enzyme Fragment Complementation system to monitor receptor-receptor interactions at the s...
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Concomitant inhibition of multiple cancer-driving kinases is an established strategy to improve the durability of clinical responses to targeted therapies. The difficulty of discovering kinase inhibitors with an appropriate multi-target profile has, however, necessitated the application of combination ther...
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We recently reported that several clinical kinase inhibitors also inhibit bromodomain epigenetic reader proteins with
therapeutically relevant potencies (Nat. Chem. Biol. (2014) doi: 10.1038/nchembio.1471). Nanomolar activity on BRD4 by BI-2536 and TG-101348, clinical PLK1 and JAK2/FLT3 kinase inhibitors, respectively, was particularly ...
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Ligand-induced receptor dimerization is the first functional step in receptor activation, representing the most proximal,
functional read-out for receptor activation. Here we present a novel application of the Enzyme Fragment Complementation system to monitor receptor-receptor interac...
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Biologics represents one of the fastest growing classes of biopharmaceutical molecules today. One of the major bottlenecks
in the development of biologics is the lack of ready-to-use bioassays for potency, stability and lot release testing.
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Neutralizing antibodies (NAbs) to biological drugs may cause loss of therapeutic efficacy and in some cases, loss of endogenous
protein function as well. Standard immunoassays can detect anti-drug antibodies, but cannot differentiate neutralizing
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Nuclear Hormone Receptor (NHR) activation is comprised of four steps: 1) ligand binding to the NHR, 2) nuclear translocation, 3) recruitment of a Steroid Receptor Coactivator Peptide (SRCP), and 4) transcriptional activation of target DNA sequence. P...
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PathHunter
® eXpress Dimerization Assay Kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to
study receptor-receptor interactions at the cell surface. The eXpress kits contain all the reagents needed for a complete assay
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PathHunter® eXpress Receptor Tyrosine Kinase (RTK) Internalization Assay kits provide a robust, highly sensitive and easy-to-use, cell-based assay for monitoring a direct and quantitative measurement of internalized RTKs localiz...
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Native Calcium GPCR Assays provide a fast, reliable method for detection of changes in intracellular calcium. Cells expressing a receptor of interest that signals through calcium are pre-loaded with a calcium-sensitive dye and then treated with compound. Upon stimulation, the receptor signals release of intracellular calcium, which results in an increase of dye...
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The tumor microenvironment consists of a complex array of interacting players including hyperproliferative malignant epithelial cells, stromal fi broblasts, activated vasculature, as well as polarized and suppressed immune cells. Understand...
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Although biologics have demonstrated utility for treatment of
rheumatoid arthritis, a significant proportion of patients fail to respond or develop dose-limiting side effects. This, together
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PathHunter® Dimerization Assays provide a robust, highly sensitive and easy-to-use cell-based functional assay to study various protein activities in a cell. The assays allow for the monitoring of receptor-receptor interactions at the&...
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DiscoveRx® has pioneered a novel enzyme complementation system to monitor cellular events such as protein translocation, protein interactions, and degradation in an HTS friendly, cell-based format. This unique technology provides a basis for the generation of novel cellular assays for intractable targets, and simplify the detection of cellular ...
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Neutralizing antibodies (NAbs) to biological drugs may cause loss of therapeutic effi cacy and in some cases, loss of endogenous
protein function as well. Standard immunoassays can detect anti-drug antibodies, but cannot differentiate neutralizing
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One of the major bottlenecks in the development of biosimilars is the need for good bioassays to create potency, stability
and neutralizing antibody (NAb) assays. Ideal bioassays need to refl ect the clinical mechanism of action (MOA) of the biopharmaceutical
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PathHunter® eXpress Nuclear Translocation assay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay for monitoring target protein translocation into the nucleus upon activation of the pathway. The eXpress kits contain everything needed for a complete experiment including cells, detection reagents, media and plat...
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PathHunter
® eXpress Cytosolic Tyrosine Kinase (CTK) Activity Assay Kits are cell-based assays used for the identification,
screening or profiling of small molecule inhibitors. This assay format cannot be used for functional testing of biologics.
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The therapeutic options for treatment of rheumatic diseases have grown and now include a variety of inflammatory pathway inhibitors, with diverse mechanisms, but having both shared and unique side effects. Understanding side effect mechanis...
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14-3-3 proteins represent a highly conserved seven-member family of ubiquitously expressed intracellular chaperonins that perform a broad range of signaling functions. The 14-3-3 eta (η) protein is an emerging diagnostic and prognostic ...
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Despite the broad range of potential treatment targets, an effective therapy does not exist for fibrosis or, for most other types of organ fibrosis. One explanation may relate to the fact that these cellular events are part of the normal wo...
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The HitHunter cAMP Assay for Small Molecules kits provide a robust, highly sensitive, and easy-to-use assay for monitoring G-protein coupled receptor (GPCR) activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells. This kit is ideal for screening and profiling small molecules. For testing biologics samples (e.g. crude biologic...
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The HitHunter cAMP Assay for Biologics kits provide a robust, highly sensitive, and easy-to-use assay for monitoring G-protein coupled receptor (GPCR) activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells. This kit is ideal for testing biologics samples (e.g. crude biologic samples in serum or plasma, purified or non-purifi...
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Compounds that bind to allosteric sites offer many benefits over those which interact orthosterically. These include enhanced specificity, ability to operate only on receptor activation and reduced risk of overdose. A number of allosteric compounds have been identified in multiple disease
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Improving the safety and efficacy of drug candidates that enter clinical development require assays that are more predictive of human outcomes. The BioMAP platform uses human primary cells to model complex aspects of disease and tissue biology and can be applied to better understand
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DiscoveRx® has pioneered a novel enzyme complementation system to monitor cellular events such as protein translocation, protein interactions, and degradation in an HTS friendly, cell-based format. This unique technology provides a basis for the generation of novel cellular assays for...
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There is increasing interest in applying in vitro methods to characterize the potential toxicity of drugs and chemicals.While data-driven approaches to build predictive models can be helpful for risk assessment, the ability to inform an in depth underst...
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1. Our goal is to develop more robust and physiologically relevant in vitro models of the host-tumor microenvironment
• Co-cultures of human primary fibroblasts or
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BioMAP システムとは、ヒトの疾患に限りなく近い微小環境のもとでの薬理反応を測定する試験化合物・物質のフェノタイプ(表現型)プロファイリング技術であります。各システムは、一連のヒトプライマリー細胞を用いて、臨床結果や論文上で報告されている直接疾患に関与しているタンパク質やサイトカイン等の発現レベルを測定するとこによって、各試験物質にユニークなタンパク質発現プロファイルを作製します。そ...
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Cell-based bioassays often pose a hurdle during a rapidly moving biologics development program. High standards for assay accuracy, precision, reproducibility and robustness are additionally put to the test by the use of continuous culture cells that can add to assay variability and increase the cost and complexity of each assay.
Advent of new technology platforms can enabl...
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We are applying a chemical biology approach for elucidating potential toxicity mechanisms for thrombosis-related side effects in humans. In previous work with the EPA for the ToxCast™ program, it was observed that several classes of chemicals, including aryl hydrocarbon receptor (AhR) agonists...
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One of the major bottlenecks in the development of biosimilars is the need for good bioassays to create potency,
stability and neutralizing antibody (NAb) assays. Ideal bioassays need to reflect the clinical mechanism of action
(MOA) of the originator drug and should be simple, precise, reproducible and robust. In additio...
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Regulatory authorities define biosimilars as drugs that are “highly similar” to or “interchangeable” with an
approved biologic. The lack of a pre-defined path to demonstrate similarity leaves the burden of proof on the
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Interest in GPCR ligand bias has increased in recent years due to evidence that positive and negative aspects of drug activity can be driven by differential pathway signaling. As a result it is possible to develop drugs with reduced side effects th...
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Cell-based bioassays often pose a hurdle during a rapidly moving biologics development program. High standards for assay accuracy, precision, reproducibility and robustness are additionally put to the test by the use of continuous culture cells tha...
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Ligand-induced receptor dimerization is the first functional step in receptor activation, representing the most proximal, functional read-out for receptor activation. It is well understood that the family of Interleukin receptors will dimerize with the other members of its family leading to a complicated signaling cascade that is critically involved in a vari...
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Antibody-dependent cell-mediated cytotoxicity (ADCC) is the mechanism by which many Class I therapeutic antibodies, including rituximab and trastuzumab, achieve clinical effi cacy. In particular, molecules based on IgG1 isotype may be expec...
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PathHunter® GPCR Bioassay kits are ready to use kits that contain everything necessary to perform a functional assay with live cells, without any continuous cell culture. This kit has been designed to rapidly detect the potency of your biologic or the presence of neutralizing antibodies against the biologic. The Bioassay kits include single use v...
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The cAMP Hunter™ GPCR Bioassay Kits provide a robust, highly sensitive and easy-to-use assay for monitoring G-protein coupled receptor (GPCR) activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells.
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PathHunter Cytokine Receptor Bioassay kits are ready to use kits that contain everything necessary to perform a functional assay with live cells, without any cell culture. This kit has been designed to rapidly detect the efficacy of your biologic or the presence of neutralizing antibodies against the biologic. The bioassay kits include single use vials ...
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PathHunter® RTK (Receptor Tyrosine Kinase) Bioassay Kits are ready to use kits that contain everything to perform a functional assay with live cells, without any cell culture. This kit has been designed to rapidly detect the efficacy of your biologic or presence of neutralizing antibodies against the biologic. The bioassay kits include single use vials of f...
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PathHunter® Dimerization Bioassay Kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study receptor-receptor interactions at the cell surface. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay ...
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PathHunter® Darbepoetin Alfa Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study darbepoetin alfa potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and ...
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PathHunter® Human Growth Hormone (hGH) Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study hGH potency and neutralizing antibodies. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilution buffer, and...
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PathHunter® Insulin Lispro Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study insulin lispro potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilution b...
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PathHunter® Aflibercept Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study aflibercept potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates...
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PathHunter Ranibizumab Bioassay kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study ranibizumab potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-valid...
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The relationship between drug efficacy and adverse events (AE) is dependent on (i) target selectivity, (ii) primary and secondary effects of target modulation and (iii) the concentration at which these interactions occur. BioMAP technology uses a systems biology approach to capture the complexity of physiologically relevant tissue microenvironments and ...
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Purpose: Our goal is to identify in vitro assays that can predict adverse effects in humans and help elucidate mechanisms of toxicity. We performed large scale screening of approved drugs and experimental chemicals across panels of human primary cell based assays and co-cultures to identify assay endpoints that may be associated with particular adverse drug r...
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DiscoveRx® has pioneered a novel enzyme complementation system to monitor cellular events such as protein translocation, protein interactions, and degradation in an HTS friendly, cell-based format. This unique technology provides a basis for the generation of novel cellular assays for intractable targets, and simplify the detection of cellular ...
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Interest in GPCR ligand bias has increased in recent years due to evidence that positive and negative aspects of drug activity can be driven by differential pathway signaling. As a result it is possible to develop drugs with reduced side effects that enhance positive effects through favoring one pathway over another. The availability of assays that can measur...
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The KILR cytotoxicity cell line enables the development of a simple, non-radioactive and dye-free method to specifically measure target cell death in a co-culture. The KILR assay has several applications in iOnc drug development including measuring target cell death through Antibody Dependent Cell-mediated Cytotoxicity (ADCC), Complement Dependent Cytotoxicity ...
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The KILR cytotoxicity cell line enables the development of a simple, non-radioactive and dye-free method to specifically measure target cell death in a co-culture. The KILR assay has several applications in Cancer Immunotherapy (iOnc) drug development including measuring target cell death through Antibody-Dependent Cell-mediated Cytotoxicity, ADCC, Complement-D...
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The PathHunter Bioassay ED Detection Kit is to be used with PathHunter Bioassays cells overexpressing ProLabel®/ ProLink™-tagged (PL/PK-tagged) reporter or target proteins, but not expressing any EA. The Bioassay ED Detection reagent itself contains the complementary EA fragment. The kit is easy-to-use and can be run in both 96-well and 384-well micro...
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PathHunter® Exendin-4 Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study exendin-4 potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. Th...
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Cell-based bioassays often pose a hurdle during a rapidly moving biologics development program. High standards for assay accuracy, precision, reproducibility and robustness are additionally put to the test by the use of continuous culture cells that can add to variability and increase the cost and complexity of each assay. This is particularly challenging for...
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Ligand-induced receptor dimerization is an early functional step in receptor activation, representing the most proximal, functional read-out for Interleukin receptors. It is well understood that the family of Interleukin receptors will dimerize with the other members of its family leading to a complicated signaling cascade that is critically involved in a var...
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Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. Therefore, therapeutics that block inhibitory receptors have proved to be powerful agents to restore anti-tumor immune responses. One key inhibitory checkpoint receptor that is the target of sev...
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Cystic fibrosis (CF) patients have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel that result in reduced membrane expression and function. CF patients have impaired lung function due to chronic airway inflammation driven by dysregulated Th17 and Th2 immune responses. These responses lead to overproduction of mucou...
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PathHunter® IL1RL1/IL1RAP Dimerization Bioassay Kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study receptor-receptor interactions at the cell surface. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist...
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Cell-based bioassays often pose a hurdle during a rapidly moving biologics development program. High standards for assay accuracy, precision, reproducibility and robustness are additionally put to the test by the use of continuous culture cells that can add to variability and increase the cost and complexity of each assay. This is particularly challenging for...
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The KILR Retroparticles provide a potent vehicle for the stable delivery of the KILR reporter construct into almost any dividing cell line, enabling the creation of KILR cytotoxicity assays in the cell line expressing the target of your choice. The KILR Cytotoxicity cell line you generate enables the development of a simple, non-radioactive and dye-free method ...
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Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. Therefore, therapeutics that block inhibitory receptors have proved to be powerful agents to restore anti-tumor immune responses. One key inhibitory checkpoint receptor that is the target of several the...
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We have developed complex in vitro co-cultures of human primary cells to model disease states in a standardized format to enable phenotypic drug screening.
The Diversity PLUS panel of 12 BioMAP systems has been validated to test agents and combinations with respect to predicting efficacy and safety.
Additional panels relevant...
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Following the recent regulatory approvals of a number of checkpoint inhibitor therapeutics, development of a wide array of immunomodulatory therapeutic antibodies targeting novel antigens and with distinct mechanisms of action (MOA) have emerged. These include classical monoclonal antibodies, but also increasingly bi- and multi-specific antibodies designed to...
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Regulation of immune responses is tightly controlled through a balance of co-stimulatory and inhibitory checkpoint receptors, often exploited by many cancers. Therefore, therapeutics that block inhibitory receptors or activate immunostimulatory checkpoint receptors have proved to be powerful agents to restore anti-tumor immune responses. However, developing d...
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PathHunter eXpress Pathway assay kits provide a robust, highly sensitive and easy-to-use method cell-based functional assay for IκB degradation and NFκB pathway activation. The eXpress kits contain everything needed for a complete IκB degradation assay including cells, detection reagents, media, and plates. The prevalidated, frozen eXpress cel...
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The PathHunter β-Arrestin2 Retroparticles includes Moloney murine leukemia retrovirus (MMLV) expressing β-arrestin2 fused to the β-galactosidase (β-gal) reporter fragment called EA (enzyme acceptor). The Retroparticles can be used for effective transduction of a wide variety of dividing target cells (e.g. CHO, HEK 293, U2OS) resulting in hig...
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Rationale. We have elucidated toxicity mechanisms of known adverse effects (AEs) associated with clinical drugs using a chemical approach in our BioMAP human primary cell-based systems modeling human tissue and disease. In previous work with the Environmental Protection Agency’s (EPA) ToxCast™ program and in downstream studies, we tested compounds...
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The PathHunter EA Parental Cell Lines are engineered cell lines that stably express a particular reporter protein fused to a large β–galactosidase (β-gal) enzyme reporter fragment called EA (enzyme acceptor). The EA parental cell lines have various cell backgrounds and are intended to be used with ProLabel®/ ProLink™-tagged proteins to...
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PathHunter® TrkC Bioassay kits provide a robust, highly sensitive, and easy-to-use, cell-based functional assay to study potency of drugs targeting Neurotrophin 3 or the TrkC receptor. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilut...
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PathHunter IGF1R Bioassay kits provide a robust, highly sensitive, and easy-to-use, cell-based functional assay to study potency of drugs targeting IGF1, IGF2, or the IGF1 receptor. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilution buffer, and assa...
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Compounds that bind to allosteric sites offer many benefits over those which interact orthosterically. These include enhanced specificity, ability to operate only on receptor activation and reduced risk of overdose. A number of allosteric compounds have been identified in multiple disease areas including CNS (physiological and neuropathic disorders), metaboli...
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The PathHunter Checkpoint Receptor Signaling Assay is a simple, highly specific assay to enable discovery and development of small molecule and biologic drugs targeting immune checkpoint receptors, belonging to the Immunoglobulin Superfamily (IgSF), such as PD-1, CD28 and ICOS.
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cAMP Hunter Follitropin Alfa Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study potency and neutralizing antibodies for Follitropin Alfa and its analogues. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist...
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The PathHunter Bioassay Detection Kit is to be used with PathHunter Bioassay cells or PathHunter Cell Lines. The kit is easy-to-use and has been successfully run in a 96-well microplate format. The resulting signal is chemiluminescent and is read with any standard plate reader.
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PathHunter Panitumumab Bioassay kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study panitumumab potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-valid...
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The InCELL Detection Kit is to be used with InCELL Pulse assays made with ProLabel expression or cloning vectors. This kit has a 96-well plate format, is easy-to-use, and results in a chemiluminescent signal that can be read with any standard plate reader.
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InCELL Pulse Cellular Target Engagement Assays are 96-well plate format kits for the assessment of inhibitor cellular potency. The assay uses DiscoverX’s proprietary enzyme fragment complementation (EFC) technology to measure compound-dependent thermal stabilization of target proteins in a cellular context. InCELL Pulse enables the measurement of quantita...
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PathHunter® eXpress Receptor Tyrosine Kinase (RTK) Activity Assay Kits are functional cell-based assays used for identification, screening or profiling of small molecule inhibitors. This assay format cannot be used for functional testing of biologics.
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pCMV Mammalian cloning vectors are intended for cloning your protein of interest (e.g. membrane protein or intracellular protein) with ePL, PK1 or PK2, as a N- or C-terminal tag, and subsequently transfecting into a parental cell line expressing an EA-tagged reporter protein (Note: in some assay formats the cells only express an ED protein and the EA protein is...
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cAMP Hunter Teriparatide Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study Teriparatide potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qu...
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PathHunter® Parathyroid Hormone (PTH) Bioassay kits are ready to use kits that contain everything necessary to perform a functional assay with live cells, without any continuous cell culture. This kit has been designed to rapidly detect the potency of your biologic or the presence of neutralizing antibodies against the biologic. The Bioassay ki...
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The InCELL Hunter™ Target Engagement Assay Kit provides a simple and easy-to-use method for building on-demand intracellular binding assays. This unique platform allows rapid generation of cell-based assays that measure quantitative changes in protein stability upon compound binding. Whether you are studying intracellular protein or lipid kinases, phospho...
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PathHunter® IL-2 Bioassay kits provide a robust, highly sensitive, and easy-to-use cell-based functional assay to study IL-2 potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre...
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PathHunter® Epoetin Alfa Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study epoetin alfa potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, an...
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PathHunter® GLP1 (7-37) Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study GLP1 (7-37) potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plat...
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PathHunter® Bevacizumab Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study bevacizumab potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates...
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PathHunter β-Arrestin cell lines are stable clonal cell lines that expedite drug discovery and development by providing robust response to over 90% of all known G-protein coupled receptor (GPCRs), with accurate pharmacology. This assay measures an essential pathway in GPCR activation, i.e. β-arrestin recruitment to activated GPCRs, enabling scientists...
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A common feature of 7TM receptors is that upon activation, the receptors are bound by cellular Arrestin proteins. DiscoveRx has pioneered the PathHunter® β-Arrestin assay platform for monitoring these events using enzyme fragment complementation (EFC) and applied this technique to develop assays for more than 170 human GPCR targets. Unlike second messenger assays that are am...
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The HitHunter® cGMP assay measures cGMP in cell lysates from cells induced in suspension in a microtiter plate.
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Screening compounds in primary human cell BioMAP® systems designed to model diseased tissues reinstates a more physiological approach to drug discovery. Here, we present BioMAP® analysis of two BTK inhibitors revealing cell-selectivity, efficacy and safety related activities. Ibrutinib is broadly active on endothelial, epithelial, smooth muscle cells and fibroblast-based systems, while ...
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PathHunter Pharmacotrafficking cell lines are based on the enzymatic fragment complementation technology. The cells are expressed as a ProLink™ (PK)-tagged mutant transmembrane protein that is retained in the endoplasmic reticulum (ER) d...
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PathHunter® Insulin Glargine Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study insulin glargine potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, diluti...
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KILR Detection Kit is to be used with the KILR Assays for Adherent or Suspension Cell Lines when running ADCC or other immune assays that result in cell lysis. The kit is easy-to-use and has been successfully run in 96-well microplate format. The resulting signal is chemiluminescent and is read with any standard plate reader.
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PathHunter® Insulin Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study insulin potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilution buffer, and ass...
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The cAMP Hunter Exendin-4 Bioassay Kits provide a robust, highly sensitive and easy-to-use assay for monitoring glucagon like peptide receptor 1 (GLP1R) activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells.
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Ligand-induced receptor dimerization is an early functional step in receptor activation, representing the most proximal, functional read-out for Interleukin receptors. It is well understood that the family of Interleukin receptors will dimerize with the other members of its family leading to a complicated signaling cascade that is critically involved in a var...
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The InCELL Pulse Target Engagement Starter Kit provides reagents and protocols for the design and development of InCELL Pulse assays for the measurement of inhibitor cellular potency against user-defined protein targets of interest. The assay applies DiscoverX’s proprietary enzyme fragment complementation (EFC) technology to measure ligand dependent therm...
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PathHunter® FGFR4-Beta-Klotho Bioassay kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study FGF-19 potency and neutralizing antibodies. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, dilution buffer, and assay...
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PathHunter CHO-K1 VIPR2 Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study drug potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qualified, ...
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PathHunter Pertuzumab Bioassay kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study pertuzumab potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qualifi...
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cAMP Hunter Liraglutide Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study Liraglutide potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qual...
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KILR CD16 Effector Cells are purified human cytotoxic T lymphocytes stably expressing CD16 (FcγRIIIa; V158 variant), produced in a standardized batch. The cells were developed for Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and T Cell Redirection (TCR) applications to reproducibly mediate target cell death.
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PathHunter U2OS MC4R Bioassay Kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study drug potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qualified, fro...
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PathHunter IL6R/IL6ST Bioassay kits provide a robust, highly sensitive, and easy-to-use cell-based functional assay to study potency of anti-IL-6R or anti-IL-6 antibodies and their neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, a...
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PathHunter Anakinra Bioassay kits provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study anakinra potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-qualified, ...
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For Chemiluminescent Detection of PD-L1-Induced PD-1 Signaling
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For Chemiluminescent Detection of Sargramostim Activity
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The PathHunter Checkpoint Signaling Assay for Tumor Necrosis Factor Receptor Superfamily (TNFRSF) members (or receptors) is a simple, highly specific assay to enable discovery and development of small molecule and biologic drugs targeting the TNFR superfamily of receptors that activate the non-canonical NF-kB pathway through NF-kB inducing kinase (NIK). The assay is a robust measurement of co-s...
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PathHunter IL17RA/IL17RC Bioassay Kits provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study receptorreceptor interactions at the cell surface. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-validated, frozen bioassay cells hav...
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The cAMP Hunter NPY2R Bioassay kits provide a robust, highly sensitive and easy-to-use assay for monitoring peptide YY activation based on 3'-5'-cyclic adenosine monophosphate (cAMP) production in cells..
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The PathHunter SIRPα Signaling Bioassay Kit provides a simple, highly specific assay to enable discovery and development of small molecule and biologic drugs targeting the CD47-SIRPα signaling axis. The bioassay kit contains all the materials needed for a complete assay, including cells, detection reagents, cell plating reagent, positive control antibody, and assay plates. The cryop...
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The ADP Quest™ Assay is a biochemical assay to measure the accumulation of ADP, a product of kinase and ATPase enzyme activity. The Assay is useful for determining substrate Michaelis-Menten kinetics and for profiling inhibitor potency and mode of action. It can be run in either an endpoint or kinetic mode and is compatible with both peptide substrates and whole proteins. The Assay is for...
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ADP Hunter™ Plus is a biochemical assay to measure the accumulation of ADP, a product of kinase enzyme activity. ADP Hunter Plus is specifically designed for high throughput screening of kinase inhibitors, and is compatible with both peptide substrates and whole proteins. The assay has been designed for research use in 384-well microplates, but can also be run in additional microplate for...
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The PathHunter TrkA-p75 Bioassay kit provides a robust, highly sensitive, and easy-to-use functional cell based assay to study drug potency and neutralizing antibodies. The bioassay kit contains all the materials needed for a complete assay, including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The cryopreserved cells have been manufactured to en...
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PathHunter Internalization Assays are cell-based assays that measure internalization of single-pass membrane receptors, e.g. receptor tyrosine kinases (ErbB-2), immune checkpoint receptors (CD33), mediated by small molecule or biologic therapeutics. Measuring drug-mediated receptor internalization can provide insight into diseases, drug tolerance, unwanted side effects and helps in identifying ...
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The ChemiSCREEN and ChemiBRITE Cell Lines are designed to enable the measurement of intracellular calcium levels when a GPCR of interest has been activated by a ligand. These cell lines are suitable for studying small molecules as well as biologics. The assay protocol has been optimized for use in either a 384-well or 96-well format.
ChemiSCREEN and ChemiBRITE cells stably expres...
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InCELL Hunter™ eXpress Assays provide a cell-based approach to evaluate changes in protein stability upon compound binding. These assay kits have been validated for use in 96-well and 384-well microplate formats. The eXpress kits contain all the materials needed for a complete assay including cells, cell plating reagents, detection reagents, and plates. The pre-validated, cryopreserved eX...
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PrecisION cell lines are designed to provide pharmacologically-relevant cell models for research and screening applications.
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SPRINTer Endogenous Protein Turnover Biosensor Cell Lines are stable clonal cell lines used for monitoring drug-induced protein turnover of a specific endogenous target. Genome engineering or editing techniques, such as CRISPR/Cas9, are used to introduce a small tag into the endogenous locus of interest. This allows for the quantitation of changes in target protein levels when cells are treated...
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PathHunter Aflibercept Bioassay HS Kit delivers a robust, highly sensitive, and easy-to-use functional cell-based assay to determine Aflibercept drug potency and detect neutralizing antibodies. This bioassay HS kit has been optimized further to deliver reproducible results with lower variability. The bioassay kit contains all the materials needed for a complete assay, including cryopreserved ce...
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PathHunter® Bevacizumab Bioassay HS Kit provide a robust, highly sensitive and easy-to-use, cell-based functional assay to study bevacizumab potency and neutralizing antibodies. The Bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-validated, frozen cells have been...
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PathHunter Ranibizumab Bioassay HS Kit provide a functional, robust, highly sensitive, and easy-to-use cell-based assay to study ranibizumab potency and neutralizing antibodies. The bioassay kits contain all the reagents needed for a complete assay including cells, detection reagents, cell plating reagent, positive control agonist, and assay plates. The pre-validated, frozen cells have been man...